Mapping the distribution of targeted chemical species in tissues is very important in many areas of biology and medicine. A useful methodology for these measurements would be one that is sensitive enough to give an accurate measure of the minute quantities of material in cells as well as possess the spatial resolution to distinguish organelles. Towards this end, Secondary Ion Mass Spectroscopy (SIMS) has inherent analytical properties to meet the need. A critical goal for an advanced SIMS instrument for ultra-fine imaging at the cellular and sub-cellular level is the development of a high-brightness ion beam probe, especially with negative oxygen ion beams, to yield ~10-20 nm resolution for a beam current of ~1 pA. The best results today fall short of these specifications by more than an order of magnitude. The experiments and design calculations in Phase I demonstrate feasibility of the overall technical objectives, and provide strong guidance for developing a credible Phase II plan during which a negative oxygen ion primary beam probe will be built, optimized and tested. The new ion beam probe being developed at FMT under this NIH-sponsored SBIR program will improve the current state-of-the art for O- beams by 1 to 1.5 orders of magnitude and allow making a quantum leap in the race for high-resolution in SIMS. Our goal is to apply the final product for spectroscopic imaging of the distribution of chemical components of cells with about 10-20-nanometer resolution. This will help cross the present technological barrier for addressing several fundamental problems in cell biology relevant to studies of carcinogenesis, toxicology, neurochemistry as well as the treatment of several diseases including cancer. While this work focuses on mapping fine-scale distribution of targeted chemical species in cancer cells, success of this project will immediately benefit a broad range of disciplines in science and technology including many other areas in biology, medicine and nanotechnology. [unreadable] [unreadable]